Vibrio cholerae is a major pathogen that has caused several cholera pandemics over the course of human history. While much is known about how the bacterium causes disease, relatively little is known about V. cholerae’s environmental lifestyle and how it evolved in the first place to acquire pathogenic potential. The organism’s natural habitat is thought to have played a pivotal role in this process and research in the Blokesch laboratory has revealed critical mechanisms at play in this context.

Our group previously deciphered the regulatory network of natural competence for transformation of Vibrio cholerae as well as the mechanistic aspects of the DNA uptake process. In the latter context, we also discovered that the central pilus part of the DNA-uptake machinery fulfills several distinctive functions including the ability to colonize chitinous surfaces under flow conditions and to recognize kin cells (see below).

We also demonstrated that when grown on chitinous surfaces V. cholerae does not solely rely on free DNA that is available in its environment. Instead, the bacterium mediates kin-discriminated effacement of neighboring bacteria using a molecular killing device known as the type VI secretion system (T6SS). Together with the pathogen’s DNA uptake potential the T6SS enhances horizontal gene transfer (HGT). Our most recent study should that this mode of HGT fosters the transfer of long  DNA stretches that frequently extend beyond 150kb. This process leads to rapid evolution.

More recently, we also started to work on the bacterium Acinetobacter baumannii and its natural competence program. A. baumannii is an opportunistic human pathogen and frequently associated with hospital-acquired infections. As this bacteria species is commonly resistant against several group of antibiotics (e.g., multi-drug resistance), it is of prime importance to better understand its HGT capacity.

Selected recent publications on this topic (for a full list of publications go here): 

  • Matthey N., Stutzmann S., Stoudmann C., Guex N., Iseli C., Blokesch M. (2019) Neighbor predation linked to natural competence fosters the transfer of large genomic regions in Vibrio cholerae. eLife 8:e48212.
  • Metzger L.C.*, Matthey N.*, Stoudmann C., Collas E.J., Blokesch M. (2019) Ecological implications of gene regulation by TfoX and TfoY among diverse Vibriospecies. Environ. Microbiol., 21:2231-2247. (*equal contribution).
  • Metzger L.C., Stutzmann S., Scrignari T., Van der Henst C., Matthey N., Blokesch M. (2016) Independent regulation of type VI secretion in Vibrio cholerae by TfoX and TfoY. Cell Rep.,15:951-958.
  • Borgeaud S., Metzger L.C., Scrignari T., Blokesch M. (2015) The type VI secretion system of Vibrio choleraefosters horizontal gene transfer. Science,347:63-67.
  • Seitz P., Blokesch M. (2013) DNA-uptake machinery of naturally competent Vibrio cholerae. Proc. Natl. Acad. Sci. USA, 110:17987-92.

The central pilus part of the DNA-uptake complex allows V. cholerae to recognize and aggregate with kin cells and to colonize chitinous surfaces under flow conditions. Current efforts in the lab aim at better understanding this process and to better characterize the chitin-attached biofilm structure. Given that past studies had identified a strong antibody response in convalescent patients against this specific pilus, we hypothesize that the kin-dependent aggregation on chitinous surfaces might contribute to the transmission of cholera in endemic areas.

Selected recent publications on this topic (for a full list of publications go here): 

  • Adams D.W., Stutzmann S., Stoudmann C., Blokesch M. (2019) DNA-uptake pili of Vibrio choleraeare required for chitin colonisation and capable of kin recognition via sequence-specific self-interaction. Nat. Microbiol., 4:1545-1557.
  • Dubnau D., Blokesch M. (2019) Mechanisms of DNA Uptake by Naturally Competent Bacteria. Annu. Rev. Genet., 53 [ePub ahead of print].
  • Metzger L.C., Blokesch M. (2014) Composition of the DNA-uptake complex of Vibrio cholerae. Mob. Genet. Elements, 4:e28142.
  • Seitz P., Blokesch M. (2013) DNA-uptake machinery of naturally competent Vibrio cholerae. Proc. Natl. Acad. Sci. USA, 110:17987-92.

More generally, we are also interested in the transmission of cholera in endemic areas. Our approach is to decipher the molecular mechanisms that are at play under infectious or environmental conditions and use this knowledge to better understand the transmission process. More recently, our lab also identified a suite of virulence factors that are required to modulate the interactions between V. cholerae and non-human hosts (e.g., aquatic amoebae). Such amoebae might serve as hosts in the environment, provide a training ground towards pathogenesis, and contribute to transmission (in a trojan horse manner).

Selected recent publications on this topic (for a full list of publications go here): 

  • Van der Henst C., Vanhove A.S., Drebes Dörr N.C., Stutzmann S., Stoudmann C., Clerc S., Scrignari T., Maclachlan C., Knott G., Blokesch M. (2018) Molecular insights into Vibrio cholerae’s intra-amoebal host-pathogen interactions. Nat. Commun., 9:3460. doi: 10.1038/s41467-018-05976-x.
  • Van der Henst C., Scrignari T., Maclachlan C., Blokesch M. (2016) An intracellular replication niche for Vibrio cholerae in the amoeba Acanthamoeba castellanii. ISME J., 10:897-910.
  • Kühn J., Finger F., Bertuzzo E., Borgeaud S., Gatto M., Rinaldo A., Blokesch M. (2014) Glucose- but not rice-based oral rehydration therapy enhances the production of virulence determinants in the human pathogen Vibrio cholerae. PLoS Negl. Trop. Dis., 8:e3347.